The Effectiveness of Outpatient Treatment Under the Control of the Soluble ST2 Receptor Concentration in Patients With Heart Failure With Reduced Ejection Fraction After Acute Decompensation of Heart Failure.

Aim    To study the effectiveness of a treatment based on monitoring the soluble ST2 receptor (sST2) concentration in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction (LVEF) after acute decompensated heart failure (ADHF).Material and methods    The study included 37 patients hospitalized for ADHF with LVEF ≤40% and sST2 concentration ≥37.8 ng/ml at the time of discharge from the hospital. Patients were randomized into two groups: a sST2 monitoring (sST2M) group (19 patients) and a standard therapy (ST) group (18 patients). The follow-up period was 12 months. At baseline, the groups practically did not differ by clinical, functional, laboratory, and instrumental characteristics. For the sST2M group, the goal was reducing the sST2 concentration by >30% of baseline or to <30 ng/ml.Results    Therapy in both groups was comparable both in doses and in frequency of administration of basic drugs. However, the diuretic therapy was more frequently adjusted in the sST2M group (3.0 [1.0; 4.0] vs. 1.0 [0; 3.0] adjustments per patient, p = 0.047), which required more visits to the clinic (7.0 [6.0; 9.0] vs. 6.0 [6.0; 6.0] visits per patient, p=0.024). In the sST2M group at 6 months, the sST2 concentration was decreased by 43.3% (p=0.001), and 13 patients (72.2%) achieved the goal. In the ST group, the sST2 concentration was decreased by 38.5% (p=0.001), and 11 patients (68.8%) reached the target values. After 12 months, the downward trend continued in both groups. In both groups, the NT-proBNP concentration decreased: in the sST2M group by 27.7% (p=0.014), and in the ST group by 31.9% (p = 0.006). By the 12th month, the decrease remained only in the sST2M group. Only the sST2M group had an increase in LVEF (+28.5%, p=0.003), a decrease in left ventricular end-systolic volume (LVESV) (-12.0%, p=0.017), and a decrease in left atrial volume (-13.4%, p=0.045); at 12 months, LVEF remained increased (26%, p=0.006), and LA volume remained decreased (-14.3%, p=0.028). Quality of life and results of 6-minute walk test (6MWT) improved in both groups. For 6 months of treatment, the sST2M group had a significantly lower incidence of composite endpoints (CEP, cardiovascular death and decompensation/hospitalization due to HF), 26.3% (5 events) of the sST2M group compared to the ST group, 83.3% (15 events) (p=0.029), primarily due to a lower incidence of decompensated HF. For 12 months of follow-up, the incidence of CEP in the ST group was 122.2% (22 events), and 47.4% (9 events) in the sST2M group (p=0.035).Conclusions    The tactics of sST2 monitoring used in the treatment of "high-risk" HFrEF patients (with high sST2 concentrations) is associated with increased LVEF, improved functional status of patients, a beneficial effect on LV remodeling, and decreased incidence of CEP.

[Effects of sacubitril/valsartan in patients with cancer therapy-related heart failure].

AIM: To evaluate the effect of Sacubitril/Valsartan (S/V) on the functional status, systolic and diastolic function of the left ventricle (LV), tolerability of therapy and to determine predictors of its effectiveness in patients with cancer therapy-related heart failure (СTRHF). MATERIALS AND METHODS: Forty patients 58 [46; 65.5] years of age with HF associated with anthracycline-containing cancer therapy were enrolled. Clinical examination, echocardiography, and assessment of potassium and creatinine levels were performed at baseline and after 6 months of S/V therapy. RESULTS: NYHA functional class (FC) improvement was observed in 22 (64.7%) patients. Radiation therapy (RT) decreased (OR 0.091; 95% CI 0.01-0.83; p=0.03) while baseline low LV EF increased (OR 9.0; 95% CI 1.78-45.33; p=0.008) the odds of FC improvement. LV EF increased from 37.3 [30; 42.5] % to 45 [38; 48] % (p<0.0001) and exceeded 50% in 7 (20.6%) patients. The odds of LV EF recovery increased when S/V therapy was initiated ≤1 year after anthracycline therapy (OR 10.67; 95% CI 1.57-72.67; p=0.0016) and decreased in patients with the history of RT (OR 0.14; 95% CI 0.02-0.89; p=0.0037) and in patients over 58 years (OR 0.07; 95% CI 0.01-0.68; p=0.022). LV diastolic function improvement included E/e' descent from 13.6 [10; 18.3] to 8.9 [6.9; 13.7] (p=0.0005), and decrease in diastolic dysfunction grade in 18 (45%) patients (p=0.0001). No significant change in serum potassium (4.45 [4.2; 4.8] versus 4.5 [4.3; 4.8]; p=0.5) and creatinine (75.4 [67.6; 85.1] versus 75.5 [68.2; 98.3]; p=0.08) levels were observed. CONCLUSION: S/V therapy is associated with improvement of EF, systolic and diastolic LV function, demonstrates a favorable tolerability profile in patients with СTRHF. Lack of RT and low baseline LV EF increased the odds of LV EF improvement; lack of RT, early (≤1 year) start of treatment after discontinuation of anthracycline therapy, and age <58 years increased the odds of LV EF recovery.

[The prognostic value of high-sensitivity C-reactive protein blood level after coronary stenting for the development of stent restenosis].

Aim      To analyze the relationship between serum concentrations of high-sensitivity C-reactive protein (hsCRP) in dynamics and development of restenosis at 12 months following elective coronary stent placement (CSP).Material and methods  The key role in atherogenesis, neointimal proliferation and restenosis belongs to inflammation. This study included 91 patients (median age, 60 [56; 66] years) with stable exertional angina after an elective CSP using second-generation stents. Follow-up coronarography was performed for 60 patients at 12 months. Concentration of hsCRP was measured immediately prior to CSP and at 1, 3, 6, and 12 months after CSP. Restenosis of the stented segment (50% or more narrowing of the stented segment or a 5-mm vessel segment proximally or distally adjacent to the stented segment) was observed in 8 patients.Results According to results of the ROC analysis, the increase in hsCRP concentration >0.9 mg/l (>25%) at one month after CSP had the highest predictive significance with respect of restenosis (area under the ROC curve, 0.89 at 95 % confidence interval (CI) from 0.79 to 0.99; sensitivity, 87.5 %; specificity, 82.8 %; р=0.0005), which was superior to the absolute value of hsCRP concentration >3.0 mg/l (area under the ROC curve, 0.82 at 95 % CI from 0.68 to 0.96; р=0.0007).Conclusion      Increased concentration of hsCRP ≥0.9 mg /l (≥25 %) at a month after CSP was associated with restenosis of the coronary artery stented segment.

The severity of internal carotid artery stenosis is associated with the circulating Th17 level.

AIM: Immune and inflammatory reactions contribute to the progression of atherosclerosis. The walls of the different arteries and segments of the arteries have heterogeneous haemodynamic and histological features. We aimed to explore the relationship between the circulating T-cell subsets and the abundance of carotid atherosclerosis in different segments of carotid arteries. METHODS: 70 patients underwent ultrasound duplex scanning to determine the degree of stenosis of the common carotid artery (CCA), the CCA bifurcation or the internal carotid artery (ICA). The blood frequencies of T-, B-, NK-cells, regulatory T cells (Treg), activated T-helpers (Th), IL10-producing Th, Th1 and Th17, as well as blood levels of hsCRP, sCD25, IL10 and IL17a were assessed. RESULTS: The frequencies of Th17 were increased in patients with ICA stenosis >35% and >50% vs. patients with ICA stenosis <35%. Th17 blood level ≥0.55 % of lymphocytes was associated with more severe stenosis of ICA (OR 4.3 (1.0-17.6), p < 0.05 for ICA stenosis of 35-50% and 6.8 (1.3-35.0), p < 0.05 for ICA stenosis >50%). BMI positively correlated with the CCA bifurcation stenosis degree (r = 0.33, p < 0.05). CONCLUSION: The severity of ICA stenosis can be associated with the circulating Th17 level.

Early diagnosis of acute renal injury in patients with acute decompensation of chronic heart failure.

AIM: To study the possibilities of previously diagnosing acute renal damage in patients with acute decompensation of chronic heart failure with reduced systolic function using biomarkers of acute renal injury. MATERIALS AND METHODS: The study included 60 patients (62.0±11.1 years) with HADS (BNP >500 pg/ml) and a reduced left ventricular ejection fraction (LV 27.05% [23.25; 32.75], c FC III-IV NYHA). The level of creatinine, urea, uric acid, albumin in serum was determined in all patients, as well as a number of biomarkers: lipocalin associated with neutrophil gelatinase (NGAL) and cystatin C (CysC) in serum; kidney damage molecule-1 (KIM-1) and angiotensinogen (AGT) in the urine. RESULTS: AKI is determined based on changes in serum creatinine concentration or diuresis value. The results obtained indicate a high specificity and sensitivity of the use of biomarkers for the diagnosis of AKI in patients with ADHF. NGAL AUC - 0.833 (p<0.001), Se - 82.8%, Sp - 4.2%. CysC AUC - 0.823 (p<0.001), Se - 79.3%, Sp - 74.2%. KIM-1 AUC - 0.782 (p<0.001), Se - 75.9%, Sp - 74.2%. AGT AUC - 0.829 (p<0.001), Se - 82.8%, Sp - 77.4%. In a multifactorial regression analysis, it was found that with NGAL greater than 157.35 ng/ml, the risk of AKI increases 13.1 times (95% CI 1.365-126.431), with an increase in KIM-1, the risk of the development of AKI increases 20.6 times (95% CI 1.802-235.524), and with an increase in AGT more than 14.31 leng/ml, the risk of AKI increases 32.8 times (95% CI 2.752-390.110). CONCLUSION: Acute kidney injury develops in 48.3% of patients hospitalized with acute decompensation of chronic heart failure. Patients with acute decompensation of chronic heart failure and AKI have significantly higher serum NGAL and CysC, KIM-1 and AGT values in the urine compared with patients without impairing renal function. These biomarkers can serve both for the early diagnosis of acute kidney damage and the prediction of AKI in patients with acute decompensation of chronic heart failure.

Multimarker Approach in Risk Stratification of Patients with Decompensated Heart Failure.

PURPOSE: to study prognostic value of various biomarkers and their combinations in patients who survived decompensation of chronic heart failure. MATERIALS AND METHODS: Patients (n=159) who were hospitalized with diagnosis of heart failure (HF) decompensation were included in a prospective single-center study. Examination on admission and the day of hospital discharge, included measurement of concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), copeptin, soluble suppression of tumorigenicity 2 (sST2), kopetin, neutrophil gelatinase-associated lipocalin (NGAL), and galectin-3. Te combined primary endpoint comprised cardiovascular (CV) death, frst hospitalization because of HF heart failure decompensation, episodes of HF deterioration which required additional i/v diuretics, and CV death with successful resuscitation. RESULTS: During one-year follow-up 56 pts (35.2%) reached the combined primary endpoint. Tere were 78 (49.1%) cardiovascular events. During hospitalization, patients with the decompensation of heart failure experienced a decrease of sST2, NT-proBNP, galectin-3, kopetin, hsTnT and an insignifcant increase of NGAL. ROC analysis identifed signifcant relation between concentrations of NT-proBNP, sST2, copeptin and, to a lesser degree, hsTnT, determined at hospital discharge, and risk of combined primary endpoint during 1-year follow-up: area under the curve (AUC) was 0.733 [95% CI 0.645-0.820], p<0.0001, 0.772 [95% CI 0.688-0.856], p<0.0001, 0.735 [95% CI 0.640-0.830], p<0.0001, and 0.659 [95% CI 0.553-0.764], p=0.005, respectively. Patients who during hospitalization did not achieve cut-off values of NT-proBNP ≤1696 rg/ml, sST2≤37.8 hg/ml, copeptin≤28.31 rmol/L and hsTnT≤28.37 rg/ml, had higher risk of reaching adverse events during 1 year; OR and 95% CI were 2.96 [1.61, 5.42] p<0.0001, 4.31 [2.34, 7.93] p<0.0001, 3.06 [1.59, 5.89] and 2.19 [2.12, 4.27]), respectively. According to Cox regression analysis, risk of the combined primary end point was the highest in patients with 3 or more elevated markers (OR = 6.6 [3.584, 12.158], p<0.0001), average in patients with 2 elevated markers (OR = 1.123 [0.51, 2.48]), p=0.7), and the lowest in patients with no markers increase or increase of only one marker (OR = 0.11 [0.049, 0.241], p<0.0001). In the Kaplan-Mayer survival analysis all three groups were statistically different. In order to identify the most prognostically strong model, a reclassifcation analysis was performed. According to this analysis, the combination of sST2 and NT-proBNP concentrations determined at hospital discharge, exceeded one NT-proBNP (reclassifcation = -8.1%). At the same time, predictive value of only sST2 just insignifcantly less than value of sST2 and NT-proBNP combination (reclassifcation = -1.9%). CONCLUSION: Patients with three and more elevated markers at hospital discharge have high risk of adverse events. Te biggest prognostic value has combination of sST2 and NT-proBNP concentrations. In order to determine the long-term prognosis of a patient with HF decompensation, it is sufcient to measure concentrations of sST2 and NT-proBNP at hospital discharge. Alternatively, it is possible to limit to sST2 only, which is just insignifcantly inferior to the sST2 and NT-proBNP combination. Patients with concentrations of sST2 ≥37.8 hg/ml and NT-proBNP ≥1696 rg/ml at hospital discharge have maximal 1year risk of death due to recurrent HF decompensation.

Low Blood Content of IL-10-Producing CD4+ T Cells as a Risk Factor for Progression of Coronary Atherosclerosis.

In a 2-year prospective study, prognostic significance of the blood content of IL-10-producing CD4+ T lymphocytes for progression of coronary artery atherosclerosis was assessed. Patients with verified stable angina (n=36) admitted for scheduled coronary angiography and coronary stenting were enrolled. The blood levels of CD4+FoxpP3+ Treg, CD4+IFNγ+ Th1, CD4+IL17+ Th17, CD4+IL10+ cells, sCD25, IL-10, IL-17, C-reactive protein, and lipoprotein (a) were assayed before endovascular interventions. The blood content of CD4+IL10+ T cells below 3.3% was associated with progression of coronary artery atherosclerosis (OR 12.0 (2.3, 61.0), sensitivity 77%, specificity 78%, p=0.003). No differences in other immunological parameters and common atherosclerosis risk factors in the groups were revealed. We hypothesize that the content of CD4+IL10+ T cells can be an important predictive marker for the progression of coronary atherosclerosis.

[Preprocedural high - sensitivity C-reactive protein (hsCRP) decrease during intensive atorvastatin therapy: the presumable impact on atherosclerosis progression after coronary stenting].

Proinflammatory status is the risk factor for coronary atherosclerosis progression after coronary stenting (CS). Intensive statin treatment is associated with hsCRP concentration decline. AIM: to evaluate prognostic significance of preprocedural hsCRP level reduction with intensive statin regimen for coronary atherosclerosis progression during one year after CS. MATERIALS AND METHODS: We enrolled 102 patients with stable angina who were on list for scheduled CS. Group I (n=37) patients received atorvastatin 80 mg for 7 days before and 3 months after CS with further dose adjustment according to LDL; group II (n=65) patients received atorvastatin 20-40 mg/day for LDL goal achievement. HsCRP level was assessed at baseline, before CS and after 1, 3, 6 and 12 months. Coronary atherosclerosis progression was defined as new ≥50% stenosis or ≥30% increase of ≥20% pre - existing stenosis according to coronary angiography (CA) 1 year after CS. RESULTS: Baseline concentration of hsCRP was comparable: 0.21 (0.13; 0.38) vs. 0.20 (0.1; 0.44) mg/dl in groups I and II, respectively (p>0.05). In group I significant hsCRP level decrease to 0.14 (0.07; 0.32) mg/dl (p.

[Neutrophil gelatinase-associated lipocalin for early diagnosis of acute kidney injury in patients with acute decompensated heart failure].

BACKGROUND: the incidence of acute kidney injury (AKI) is high in patients with acute decompensated heart failure (ADHF) and is linked with increased morbidity and mortality rates. Predictive biomarkers of AKI could allow improve outcomes in AKI. PURPOSE: to evaluate the value of serum neutrophil gelatinase-associated lipocalin (NGAL) concentrations for early diagnosis of AKI in patients with ADHF with left ventricular (LV) systolic function. METHODS: we enrolled 60 men (average age was 62.0±11.1 years) hospitalized with ADHF with reduced LV systolic function (LV ejection fraction (LVEF).

Pathological Remodeling of the Myocardium in Chronic Heart Failure: Role of PGC-1α.

Pathological remodeling of the myocardium in chronic heart failure includes the development of pathological cardiac hypertrophy, reactivation of the fetal genetic program, and disorders in cardiac energy metabolism. Coactivator-1α of receptor γ activated by peroxisome proliferator (PGC-1α), a transcription coactivator of nuclear receptors and metabolism master regulator, plays an important role in cardiac metabolism regulation. Studies on the animals models of chronic heart failure have demonstrated the development of pathological cardiac hypertrophy, metabolic disorders, and reactivation of the fetal genetic program; these processes are mutually related. An important role in regulation of these processes belongs to PGC-1α; its low expression indicates low activity and down-regulation of this coactivator. Pathological cardiac hypertrophy, decrease of PGC-1α activity, and reactivation of the fetal genetic program in chronic heart failure are demonstrated.

Head to Head Comparison of Suppression of Tumorogenicity 2 and Copeptin Significance for Prognosis of Patients After Acute Heart Failure Decompensation.

PURPOSE: To assess the suppression of tumorogenicity 2 (ST2) and copeptin significance for risk stratification of patient (pts) with acute decompensated heart failure (ADHF) during long-term follow-up compared with traditional risk factors. METHODS: We included in a prospective study 159 pts with ADHF. Blood samples to determine copeptin, sST2, NT-proBNP and hsTnT concentration were collected at admission and at discharge from the hospital. Serial determination of biomarker concentration was performed at 3, 6 and 12 months of follow-up. The combined primary end point of the trial included cardiovascular (CV) death, hospitalization due to HF, episodes of HF deterioration requiring additional intravenous diuretics and CV death with successful resuscitation. RESULTS: During 1-year follow-up (295.3±113.2 days) 56 pts (35.2%) had 78 (49.1%) cardiovascular events. Biomarker concentrations in low risk pts (without CV events) were significantly lower compared with high risk pts (with CV events). Discharge copeptin and NT-proBNP values were comparable for pts risk stratification: AUC=0.727 (95% CI 0.637-0.816), р.

Clinical significance of serial biomarkers activity determination after acute heart failure decompensation: sST2 NT-proBNP role during long-term follow-up.

AIM: Monitoring of concentrations of modern biomarkers to evaluate the efficacy of long­term treatment of patients after acute decompensated HF (ADHF). MATERIALS AND METHODS: The study included 100 patients with severe decompensated FC II-IV CHF and LV EF <40 % due to IHD, DCMP or AH. At discharge from the hospital, patients were divided into groups of low (NT­proBNP<1400 pg / ml) (control, n=30) and high (NT­proBNP≥1400 pg / ml) risk (n=70). Patients at high risk were randomized to two treatment groups, a group of NT­proBNP monitoring (NPM) (n=35) and a group of standard therapy (n=35). At the end of the study, noncompliant patients were isolated from these two groups into a separate group (n=10). The aim of the treatment was decreasing the NT­proBNP concentration to less than 1000 pg / ml and / or ≥50 % of the baseline level. In addition to the soluble suppression of tumorigenicity 2 (sST2) receptor, concentrations of copeptin, neutrophil gelatinase associated lipocalin (NCAL), galectin 3, and high­sensitivity troponin T were measured at discharge from the hospital (baseline) and at three and 6 months of treatment. RESULTS: The strongest correlations were found between changes in concentrations (Δ%) of NT­proBNP, copeptin, and sST2 and changes in CHF FC, 6­min walk distance, CCS, quality of life, LV EF, and Е / Е' (р<0.001). The incidence of cardiovascular events was directly related with the degree of decrease and / or increase in biomarker concentration. Patients of the NPM group had the lowest risk of adverse clinical outcome upon a decrease in NT­proBNP <988.5 pg / ml at 6 months of treatment or > 50 % of the baseline level at discharge from the hospital. For these patients, the mean Δ% was 60.7±8.5 % for NT­proBNP, 34.03±17.6 % for sST2, and 32.41±8.8 % for copeptin [OR at 95 % CI 0.08 (0.02-0.36), р <0.0001]. A significant increase in the risk for cardiovascular events was observed only at a considerable increase in NT­proBNP >50 % [OR at 95 % CI 3.8 (1.13-13.0), р=0.03], and the highest incidence of cardiovascular events was observed in the group of noncompliant patients (110 %). Besides NT­proBNP, to significantly decrease the risk of cardiovascular events, it was necessary to achieve a decrease in sST2 concentration to less than 30 ng / ml or by more than 24.9 % (Δ%) at the end of followup [ОR (95 % CI: 0.1 (0.02-0.5), р=0.004]. CONCLUSION: Among the modern biomarkers, changes in NT­proBNP, sST2, and copeptin concentrations most accurately reflect changes in the clinical and functional status, quality of life, and EchoCG parameters in HF patients during long­term monitoring. The lowest risk for adverse clinical outcomes was observed in post­decompensation patients with a decrease in NT­proBNP <988.5 pg / ml after 6 months of treatment or ≥50 % of baseline upon discharge from the hospital. The sST2 concentration has to be reduced by more than 24.9 % of baseline and less than 30 ng / ml in the course of long­term treatment after decompensated HF.

[Analysis of Urine Proteome in Patients With Postinfarction Cardiosclerosis Combined With Hypertensive Disease for Assessing Endothelial Dysfunction].

In our study urine protein composition of 18 healthy volunteers was compared with that of 18 patients with ischemic heart disease and concomitant hypertension. Liquid chromatography-mass-spectrometry (LC-MS) analysis of the second fraction of morning urine was carried out using nano-line high performance liquid chromatograph and hybrid mass spectrometer. The analysis revealed 23 proteins expressed in the endothelium, according to the information contained in the database Bgee, and 49 proteins, with direct functional link with the processes in the endothelium in the reconstruction of associative networks using ANDSystem program. Comparison of urine proteome of healthy people and patients with postinfarction cardiosclerosis revealed proteins specific for patients with cardiovascular disease. Thus, proteins vitronectin, syndecan-4, a histidine rich glycoprotein, endothelial protein C receptor, colony stimulating factor, cathepsin D and sekretogranin-1 may be considered as potential markers for cardiovascular diseases. Further research in this area should be conducted for clinical and experimental verification of these hypotheses.

[Soluble Suppression of Tumorogenicity 2 Increases Opportunities for Risk Stratification After Acute Heart Failure Decompensation].

PURPOSE: to evaluate the significance of soluble ST2-receptor (sST2) concentrations in patient (pts) risk stratification in with acute decompensated heart failure (ADHF) during long-term follow-up period. METHODS: In the prospective single-center study were included 159 pts with ADHF III-IV FC NYHA. Blood samples to determine NT-proBNP, sST2, hsTnT concentration were collected at the admission and at discharge from the hospital, and after 3, 6 and 12 months of follow-up. The combined primary end point of the trial included cardiovascular (CV) death, hospitalization due to HF, episodes of HF deterioration needed additional i/v diuretics and CV death with successful resuscitation. RESULTS: At admission all pts had elevated biomarker concentrations: NT-proBNP - 3615.5 (1578.0; 6289.3)pg/ml, sST2 - 60,49 (41.95; 92.87) ng/ml, hsTnT - 29.95 (21.85; 49.63) pg/ml; and at discharge: NT-proBNP - 2165.5 (982.7; 4221,2) pg/ml (%=-38,27 (-49.7; -24.34)%, p<0.0001), sST2 - 38.43 (24.67; 63.72) ng/ml (%=-30,13 (-42,07; -17,64)%, p<0,0001), and hsTnT - 28,37(21.29; 46.6) pg/ml. During 1-year follow-up 56 pts (35.2 %) had 78 (49.1%) cardiovascular events. Biomarker concentrations in low risk pts (without CV events) were significantly lower compared with high risk pts (who have CV events). At the discharge NT-proBNP and sST2 concentrations had the most predictive capacity relatively the primary end point during 1-year follow-up: AUC=0.727 (95% CI 0.637-0.816), <0,0001, and AUC=0,768 (95% CI 0.682-0.854), <0.0001, respectively. Maximally sST2 values were predictive for 180 days period of follow-up: AUC=0,809 (95% CI 0.726-0.921; <0,0001). Lack of NT-proBNP and sST2 concentrations decrease below 1696 pg/ml and 37.8 ng/ml respectively were associated with the highest risk of CV events (HR 4.41 [95% CI 1.41-9.624], p<0,0001 and HR 6.755 [95% CI 3.026- 15.082], p<0.0001, respectively). Changes of sST2 concentration during the period of pts hospitalization were also prognostically important, AUC=0.696 (0.596-0.796); p<0.0001. And pts with insufficient degree of sST2 concentrations reduction during the period of hospitalization (% <-28,3%) had the worst short-term and long-term prognosis [HR 3.68 (95% CI 2.05-6.64), p<0.0001]. Values of sST2 at the discharge were the most significant independent predictor of CV events in long-term follow-up (=0.519, p<0.0001). 91,8% of pts without CV events in the study had sST2 and NT-proBNP levels below 37.8 ng/ml and 1696 pg/ml respectively after 3, 6 and 12 months of follow-up. CONCLUSION: The values of soluble ST2-receptor over 37.8 ng/ml and NT-proBNP over 1696 pg/ml at the discharge from the hospital reflects the adverse prognosis in patients with ADHF. Serial determination of sST2 and NT-proBNP concentrations after discharge from the hospital indicates the necessity of reduction the levels of these biomarkers below the cut-off values (<37.8ng/mL and <1696pg/ml respectively) in pts with ADHF in long-term follow-up period.

[Elevated Level of the Natriuretic Peptide Among Adult Population in Regions Participating in the ESSE-RF Study and Its Association With Cardiovascular Diseases and Risk Factors].

AIM: to study associations between elevated blood plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP), risk factors and cardiovascular diseases (CVD) in samples of adult population of Russian Federation (RF) aged 25-64 years. MATERIALS AND METHODS: We analyzed data of examination of representative samples of population of 5 regions of RF obtained within the framework of the multicenter ESSE-RF study (2012-2013). Number of examined subjects was 8 077 (3 176 men). Methods included use of standard questionnaire, measurements of height, body mass, blood pressure (BP), and plasma NT-proBNP level. The following CVD were included into analysis: arterial hypertension (AH), ischemic heart disease (IHD), atrial fibrillation (AF), and stroke. RESULTS: Women compared to men had higher NT-proBNT concentration was higher in women compared to men, in both genders it rose with age. Overall 17.9 % of examinees had elevated NT-proBNT levels (14.2 and 20.3 % among men and women, respectively). Elevated NTproBNP level was associated in men with age, myocardial infarction, angina pectoris, ischemic ECG changes, left ventricular hypertrophy, AF, bradycardia, smoking, in women with age, IHD, ischemic ECG changes, AF, bradycardia, heart rate ≥80 bpm, BP ≥160/95 mm Hg. CONCLUSION: In studied RF population elevated NT-proBNP level was significantly associated with gender, age, smoking, and CVD.

[Head to Head Comparison of Suppression of Tumorogenicity 2 and Copeptin Significance for Prognosis of Patients After Acute Heart Failure Decompensation].

PURPOSE: To assess the suppression of tumorogenicity 2 (ST2) and copeptin significance for risk stratification of patient (pts) with acute decompensated heart failure (ADHF) during long-term follow-up compared with traditional risk factors. METHODS: We included in a prospective study 159 pts with ADHF. Blood samples to determine copeptin, sST2, NT-proBNP and hsTnT concentration were collected at admission and at discharge from the hospital. Serial determination of biomarker concentration was performed at 3, 6 and 12 months of follow-up. The combined primary end point of the trial included cardiovascular (CV) death, hospitalization due to HF, episodes of HF deterioration requiring additional intravenous diuretics and CV death with successful resuscitation. RESULTS: During 1-year follow-up (295.3±113.2 days) 56 pts (35.2%) had 78 (49.1%) cardiovascular events. Biomarker concentrations in low risk pts (without CV events) were significantly lower compared with high risk pts (with CV events). Discharge copeptin and NT-proBNP values were comparable for pts risk stratification: AUC=0.727 (95% CI 0.637-0.816), р.

[Lipoprotein(a), its autoantibodies, and circulating T lymphocyte subpopulations as independent risk factors for coronary artery atherosclerosis]. / Lipoproteid(a), autoantitela k nemu i tsirkuliruyushchie subpopulyatsii T-limfotsitov kak nezavisimye faktory riska ateroskleroza koronarnykh arterii.

AIM: To study the role of lipoprotein(a) [Lp(a)] as a potential autoantigen causing the activation of immunocompetent cells in atherosclerosis. SUBJECTS AND METHODS: A total of 104 men with stable coronary artery (CA) disease and different degrees of progressive coronary atherosclerosis were examined. Clinical blood analysis was carried out and lymphocyte subpopulations (CD4+, Th1, Th17, and Treg) were determined using immunofluorescence and flow cytometry. In addition, the indicators of blood lipid composition, Lp(a), autoantibody (autoAb) titer to Lp(a), and low-density lipoproteins (LDL), and the lymphocyte activation marker sCD25 were also measured. RESULTS: The Lp(a) level was shown to predict the severity of CA lesions (ß=0.28, p<0.05), regardless of age, the level of cholesterol, different T-lymphocyte subpopulations, sCD25, and autoAb. A combination of the concentration of Lp(a) above 11.8 mg/dl, that of Th17 over 11.4∙103 cells/ml and the reduced levels of regulatory T cells and IL-10-producing CD4+ T cells showed a manifold increase in the risk of severe and progressive CA atherosclerosis. There was a direct correlation of the blood level of Th1 with that of IgG autoAb specific to all atherogenic apoB-containing lipoproteins, including Lp(a). There was an inverse correlations of the lymphocyte activation marker sCD25 with IgM anti-Lp(a) autoAb titers (r=-0.36; p<0.005), but this was less significant with autoAbs to native and oxidized LDL (r=-0.21 and r=-0.24; p<0.05, respectively). CONCLUSION: The slightly elevated Lp(a) concentration along with changes in the level of T lymphocyte subpopulations was first shown to significantly potentiate the risk of progressive and multiple CA lesion in the examinees. The correlation of IgM anti-Lp(a) autoAb with the lymphocyte activation marker sCD25 and that of IgG anti-Lp(a) autoAb with Th1 have demonstrated that Lp(a) is involved in the autoimmune inflammatory processes in atherosclerosis.

[Changes in the receptor activity of ß2-adrenoreceptors of human T-lymphocytes under the effect of ß2-agonists].

Changes in the activity of ß2-adrenergic receptors of human T-lymphocytes under the effect of salbutamol (a short-acting ß2-agonist) have been evaluated with a new modified radioligand method utilizing [^(125)I]cyanopindolol and a specific ligand ICI 118551. In healthy volunteers, the receptor activity decreased after 30 min upon the inhalation of salbutamol and restored to the initial level after 2 h. At the same time, there were changes in the transcription level of the ADRB2 gene, which encodes the protein component of the ß2-adrenoreceptor. The dynamics of ß2-adrenergic receptor activity of T-lymphocytes after salbutamol treatment in patients with cardiorespiratory pathology significantly differed from that in healthy volunteers.

[Therapy of High Risk Patients After Decompensation of Heart Failure Under NT-proBNP Control. Main Results].

AIM: to compare efficacy of treatment of high risk patients after acute decompensation (AD) of chronic heart failure (CHF) based on monitoring of NT-proBNP concentration and standard treatment. MATERIAL AND METHODS: Patients (n=100) with class III-IV CHF and left ventricular ejection fraction (LV EF) <40% due to ischemic heart disease (IHD), dilated cardiomyopathy (DCMP), or arterial hypertension (AH) after compensation of HF before discharge were distributed into groups of low (NT-proBNP <1400 picog/ml, n=30) or high (NT-proBNP more or equal 1400 picog/ml, n=70) risk. High risk patients were randomized into 2 treatment groups: NT-proBNP based (group I, n=35) and standard (group II, n=35) therapy. At study closure we formed another group consisting of group I and II participants noncomplaint with study protocol (group NC, n=10). Groups practically did not differ by main clinical functional characteristics. Aim of treatment was lowering of NT-proBNP level below 1000 picog/ml or more or equal 50% from baseline. At discharge median NT-proBNP concentration was 3750.0 (2224.0; 6613.0), 2783.0 (2021.5; 4827.5), and 2162.0 (1684.5; 5750.0) picog/ml in groups I, II, and NC, respectively (=0.315). RESULTS: At study entry all group I and II patients received combination of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, -adrenoblockers, antagonists of mineralocorticoid receptors. After 6 months changes of doses of neuro-hormonal modulators in group I were more pronounced than in group II. NT-proBNP concentration decreased by 53% down to 1585.5 (976,6; 2742,5) picog/ml, =0.001, and by 10.2% in groups I and II, respectively (between group =0.001). In group I compared with II we observed more pronounced improvement of clinical functional indicators, quality of life, and parameters of systolic and diastolic LV function (<0.05), fewer cardiovascular deaths (4 vs. 10, =0.033) and repeat decompensations and rehospitalizations because CHF (4 vs. 14, =0.007). CONCLUSION: Compared with standard therapy long-term NT-proBNP guided treatment of high risk patients significantly significantly decreased rate of CV deaths and repeat decompensations and rehospitalizations because CHF, and more effectively influenced clinical and functional state, quality of life and main echocardiographical parameters of LV systolic and diastolic function.

[Level of Soluble Receptor for Glycation End-Products in Patients With Restenosis After Coronary Artery Stenting].

The purpose of research - the study of the level of soluble receptor for advanced glycation end products (CNG) in patients with coronary heart disease (CHD) with angina pectoris who have emerged restenosis after implantation of drug-eluting stents.